We have demonstrated that the collagen antagonist D-penicillamine reduces radiation-induced pulmonary fibrosis in rats exposed to single doses of 60Co gamma rays. The present work will expand the original model to more clinically relevant experimental conditions, i.e. to determine whether penicillamine can modify lung damage produced by fractionated irradiation, and to determine whether this drug can modify the radiation tolerance of tumor-bearing lung. Finally, we will determine whether penicillamine can ameliorate pulmonary injury induced by a combination of bleomycin and thoracic irradiation. Histologic, morphometric, ultrastructural, biochemical, radiographic and functional endpoints will be employed to monitor pulmonary status.